Each team booked their place in this competition through winning the Italian and Austrian titles last season, and both teams have started equally positively this time around.
Match preview
On the back of draws against Atalanta BC and Sassuolo, some will claim that AC Milan have been far from their best during the opening weeks of their Serie A title defence.
However, Stefano Pioli's team have outperformed many of their rivals while extending their unbeaten league record to 21 matches, their most recent setback coming all the way back in January.
I Rossoneri also head into this fixture having come through a five-goal thriller with neighbours Inter Milan, battling back from an early deficit to post a 3-2 win.
Rafael Leao, after late speculation regarding his future, netted a double to take him to five goal contributions this season, while Olivier Giroud also chipped in with yet another important strike.
Although Milan have been outstanding on the domestic front over the past 13 months, Piolo is aware that he must deliver on the European stage after their dismal group-stage exit in 2021-22.
Pioli will also understand the challenge which awaits his side with Red Bull Salzburg motivated to move their domestic dominance into continental competition.
The Austrian giants made the breakthrough in the Champions League last season, reaching the last 16 to post a 1-1 draw with Bayern Munich in the first round of their knockout tie before being blown away at the Allianz Arena.
While Matthias Jaissle and his squad deserved huge praise for progressing through a group which featured Lille, Sevilla and Wolfsburg, expectation levels are now higher, particularly with RB Leipzig-bound Benjamin Sesko remaining in the squad for this campaign.
So far in 2022-23, some of his teammates have taken centre stage, but the young Slovenian will relish the opportunity to perform on the biggest stage.
Salzburg head into this encounter on a five-match winning streak in the Bundesliga, keeping clean sheets in their most recent three fixtures.
Red Bull Salzburg form (all competitions):
AC Milan form (all competitions):
Team News
While Pioli will give consideration to rotating members of the starting lineup from the weekend, he is unlikely to overly tinker with a side which have just prevailed in the derby.
Brahim Diaz and Alexis Saelemaekers are both alternatives in a creative position if Giroud drops down to the substitutes' bench.
Ante Rebic may come back into the squad after suffering a minor injury against Sassuolo, but Alessandro Florenzi remains on the sidelines.
Given the form of Noah Okafor and Fernando, Sesko could have to make do with a spot on the Red Bull Salzburg substitutes' bench.
Jaissle may be prepared to select the same team which posted a 2-0 win over WSG Tirol on Saturday, with Strahinja Pavlovic having to remain patient for an opportunity in the defence after his summer move from Monaco.
Red Bull Salzburg possible starting lineup:
Kohn; Dedic, Solet, Wober, Ulmer; Capaldo, Seiwald, Kjaergaard; Kameri; Fernando, Okafor
AC Milan possible starting lineup:
Maignan; Calabria, Kalulu, Tomori, Hernandez; Tonali, Bennacer; Messias, De Ketelaere, Leao; Giroud
We say: Red Bull Salzburg 1-2 AC Milan
Despite the difference in profile, this has all the makings of being a competitive fixture, one which the home side may end with a share of the spoils. Nevertheless, Milan's superior quality in the final third may shine through, leading us to predict a narrow victory for the Serie A champions.